Coronary artery bypass graft (CABG) surgery is an increasingly common treatment for ischemic heart disease. In this procedure, a reversed segment of the patient's own saphenous vein or internal mammary artery is anastomosed between the ascending aorta and one or more stenotic coronary arteries. The anastomosis allows blood from the aorta to bypass atherosclerotic occlusions in the coronary vessels that are producing myocardial ischemia and symptoms of angina.
CABG surgery is performed with the assistance of a heart-lung machine, which temporarily performs the gas exchange function of the lungs and the blood pumping function of the heart. Use of this machine in cardiac surgery is referred to as cardiopulmonary bypass (CPB), and it allows the heart to be arrested (using cardioplegia) during the surgery while blood is shunted through a venoarterial bypass circuit. This circuit performs extracorporeal oxygenation of the blood, and returns it to the arterial tree, bypassing the heart and the pulmonary circulation. CPB allows the surgeon to operate in a bloodless field on a motionless heart.
Although CABG surgery (and use of CPB) have substantially improved the therapeutic outcome of patients with advanced myocardial ischemia, this surgery still has several undesired consequences. Technetium pyrophosphate studies have shown that perioperative myocardial infarctions occur in 21-31% of all CABG patients. Even more highly sensitive Indium-111 monoclonal antibody scintigraphy has shown that perioperative myocardial damage was present in 82% of uncomplicated CABG surgeries. Such damage is particularly troublesome in patients who have unstable angina and already compromised myocardium, because this perioperative damage can further impair heart function.
Induction of anesthesia is complicated in patients with coronary artery disease (CAD) because inhalational anesthetic agents can induce hemodynamic swings in already myocardially compromised patients. Perioperative arrhythmias can complicate the postoperative recoveries of between 20% and 30% of patients following CABG surgery. Some of these events may be due to endogenous catecholamine release caused by the stress of surgery. Although beta adrenergic antagonists (such as propranolol) have long been known to block catecholamine mediated adrenergic responses, use of beta adrenergic antagonists in heart patients has long been viewed with caution. Traditional medical teaching has been that beta adrenergic antagonists are negative inotropes, which decrease the contractility of the heart muscle. Beta adrenergic antagonists (also known as beta blockers) have therefore been used cautiously in patients who have myocardial compromise.
High doses of beta adrenergic antagonists have been assiduously avoided intraoperatively in CABG patients prior to CPB, because conventional medical teaching has been that beta blockers will cause undesirable myocardial depression. Such myocardial depression has been considered particularly unwise in CPB because it has been thought to increase the difficulty of weaning a patient from CPB. Beta blockers have been thought to interfere with the pharmaceutical action of inotropic drugs, such as dopamine or epinephrine, that may be needed to wean a patient from the heart lung machine.
Yet another problem encountered after CABG surgery is neurological or neuropsychiatric compromise. About 2-6% of cardiac surgery patients sustain unequivocal neurologic injury (such as a frank stroke) in the perioperative period. As many as 30-60% of adult cardiac surgery patients experience more subtle neurologic abnormalities or neuropsychiatric changes. About 20-30% of patients still exhibit measurable decrements in neuropsychiatric performance six months postoperatively. These changes may be caused by platelet/fibrin thrombi, which can be directly observed in the retinal vasculature. These changes may also be a consequence of the hypercoagulable status of platelets often found in patients with coronary artery disease (CAD), and of the body's immune response to the CPB circuit. Neurological insult can also be caused by air microemboli or platelet thrombi that produce cerebral ischemia in the metabolically active tissue of the brain.
Another problem that has been observed with CPB is the initiation of an inflammatory response, apparently from the contact of blood with the CPB circuit. This response results in complement and platelet activation, with attendant formation of platelet-fibrin microemboli or platelet aggregation. These responses can produce tissue micro-ischemia, that results in ischemia and infarction in myocardial, cerebral, retinal or other types of tissue. The non-specific inflammatory nature of the CPB inflammatory response can also worsen patient outcome, and slow post-operative recovery.
It is accordingly an object of this invention to provide a method of performing CPB which reduces myocardial and other types of perioperative tissue ischemia and infarction.
Another object of the invention is to provide such a method that reduces tissue injury that may occur as a result of ischemia or infarction.
Yet another object of this invention is to provide an inexpensive and convenient intervention that can improve the outcome of patients undergoing CABG surgery, reduce postoperative morbidity, and minimize the cost of such surgery by decreasing the duration of intensive care unit and hospital stays.